It has been well established that stress may substantially affect the homeostatic regulation of the immune system. In most animal models studied thus far, stressful triggers such as fear, maternal deprivation, social threat, or physiological challenge have been shown to induce immunosuppression associated with increased susceptibility to allergies and infectious diseases. These effects are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, a complex network linking the nervous, endocrine and immune systems. The HPA axis can be triggered by stress or by proinflammatory cytokines (e.g. IL-1, IL-6, and TNF-α) to ultimately result in the secretion of corticosterone (CORT) from the adrenal glands to the circulation.
CORT, in turn, acts to suppress the activation, proliferation, and trafficking of immune cells and plays a role in autoimmune regulation via shifting from Th1/Th17 pro-inflammatory to Th2 antiinflammatory responses. Indeed, previous studies have shown that rats producing lower CORT levels (e.g. due to genetic manipulation or adrenalectomy) are more susceptible to pathogenic autoimmunity. CORT is therefore often used as an immunosuppressor in the clinical treatment of inflammatory and autoimmune diseases.
Regardless of the immunosuppressive effects of CORT, chronic exposure to stress has also been linked with relapse of autoimmune diseases such as multiple sclerosis and psoriasis. Paradoxically, these diseases are characterized by a Th1/Th17 pro-inflammatory immune response, which implies that chronic stress exposure attenuates the immunosuppressive effects of CORT. It has also been suggested that CORT may affect regulatory T (Treg) cells which play a central role in protecting against autoimmune diseases.